In this project, "Haplotype analysis of candidate genes for human pigmentation," we seek to understand the relative contribution of allelic variations of candidate genes responsible for variation in human pigmentation. Pigmentation is a classic anthropological trait that has been studied objective using reflectance spectroscopy for over 50 years. Skin pigmentation is likely the trait that shows the largest degree of variability among human populations suggest the action of natural selection. The study of skin pigmentation exist among human populations suggests the action of natural selection. The study of skin pigmentation can help address many problems ranging from understanding skin cancer susceptibility, tanning and sun-burns, and the evolution of light and dark skin. The identification of the genes that determine normal within-population variation in pigmentation and differences between populations is the first essential step in the elucidation of the molecular history of human pigmentation. Combined genetic and epidemiological research on the African American population may reveal potential genetic factors involved in human pigmentation due to the wide range in both genetic and phenotypic variation in this population. This project seeks to provide a better understanding of gene, gene-gene (epistasis), and gene-environment effects on skin color. The goals of this project are to (1) ascertain a cohort of 800-1000 African Americans well-characterized for levels of eumelanin and tanning potential from the Washington, DC metropolitan area; (2) use state-of-the-art DHPLC technology to provide a formal evaluation of single nucleotide polymorphism (SNP) variation in 13 candidate genes for skin color; (3) genotype relevant SNPs within candidate genes and construct haplotypes; (4) exploit the evolutionary history of candidate gene haplotypes in order to determine if haplotypic differences account for phenotypic variation in skin color, and tanning potential; (5) assess whether gene-gene and gene-environment interactions exist by examining if skin color variation is modified after stratification of genetic and/or environmental factors; and (6) determine if molecular signatures for selection are evident across haplotypic backgrounds.